Lipidomic Typing of Colorectal Cancer Tissue Containing Tumour-Infiltrating Lymphocytes by MALDI Mass Spectrometry Imaging

Predicting the prognosis of colorectal cancer (CRC) patients remains challenging and a characterisation of the tumour immune environment represents one of the most crucial avenues when attempting to do so. For this reason, molecular approaches which are capable of classifying the immune environments...

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Main Authors: Vanna Denti, Allia Mahajneh, Giulia Capitoli, Francesca Clerici, Isabella Piga, Lisa Pagani, Clizia Chinello, Maddalena Maria Bolognesi, Giuseppe Paglia, Stefania Galimberti, Fulvio Magni, Andrew Smith
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/11/9/599
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author Vanna Denti
Allia Mahajneh
Giulia Capitoli
Francesca Clerici
Isabella Piga
Lisa Pagani
Clizia Chinello
Maddalena Maria Bolognesi
Giuseppe Paglia
Stefania Galimberti
Fulvio Magni
Andrew Smith
author_facet Vanna Denti
Allia Mahajneh
Giulia Capitoli
Francesca Clerici
Isabella Piga
Lisa Pagani
Clizia Chinello
Maddalena Maria Bolognesi
Giuseppe Paglia
Stefania Galimberti
Fulvio Magni
Andrew Smith
author_sort Vanna Denti
collection DOAJ
description Predicting the prognosis of colorectal cancer (CRC) patients remains challenging and a characterisation of the tumour immune environment represents one of the most crucial avenues when attempting to do so. For this reason, molecular approaches which are capable of classifying the immune environments associated with tumour infiltrating lymphocytes (TILs) are being readily investigated. In this proof of concept study, we aim to explore the feasibility of using spatial lipidomics by MALDI-MSI to distinguish CRC tissue based upon their TIL content. Formalin-fixed paraffin-embedded tissue from human thymus and tonsil was first analysed by MALDI-MSI to obtain a curated mass list from a pool of single positive T lymphocytes, whose putative identities were annotated using an LC-MS-based lipidomic approach. A CRC tissue microarray (TMA, <i>n</i> = 30) was then investigated to determine whether these cases could be distinguished based upon their TIL content in the tumour and its microenvironment. MALDI-MSI from the pool of mature T lymphocytes resulted in the generation of a curated mass list containing 18 annotated <i>m</i>/<i>z</i> features. Initially, subsets of T lymphocytes were then distinguished based on their state of maturation and differentiation in the human thymus and tonsil tissue. Then, when applied to a CRC TMA containing differing amounts of T lymphocyte infiltration, those cases with a high TIL content were distinguishable from those with a lower TIL content, especially within the tumour microenvironment, with three lipid signals being shown to have the greatest impact on this separation (<i>p</i> < 0.05). On the whole, this preliminary study represents a promising starting point and suggests that a lipidomics MALDI-MSI approach could be a promising tool for subtyping the diverse immune environments in CRC.
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spelling doaj.art-c6fabe7bda104c5c990099a35c223bab2023-11-22T14:11:36ZengMDPI AGMetabolites2218-19892021-09-0111959910.3390/metabo11090599Lipidomic Typing of Colorectal Cancer Tissue Containing Tumour-Infiltrating Lymphocytes by MALDI Mass Spectrometry ImagingVanna Denti0Allia Mahajneh1Giulia Capitoli2Francesca Clerici3Isabella Piga4Lisa Pagani5Clizia Chinello6Maddalena Maria Bolognesi7Giuseppe Paglia8Stefania Galimberti9Fulvio Magni10Andrew Smith11Department of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, ItalyDepartment of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, ItalyBicocca Bioinformatics Biostatistics and Bioimaging B4 Center, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, ItalyDepartment of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, ItalyDepartment of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, ItalyDepartment of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, ItalyDepartment of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, ItalyDepartment of Medicine and Surgery, Anatomy and Pathology, University of Milano-Bicocca, 20900 Monza, ItalyDepartment of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, ItalyBicocca Bioinformatics Biostatistics and Bioimaging B4 Center, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, ItalyDepartment of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, ItalyDepartment of Medicine and Surgery, Proteomics and Metabolomics Unit, University of Milano-Bicocca, 20854 Vedano al Lambro, ItalyPredicting the prognosis of colorectal cancer (CRC) patients remains challenging and a characterisation of the tumour immune environment represents one of the most crucial avenues when attempting to do so. For this reason, molecular approaches which are capable of classifying the immune environments associated with tumour infiltrating lymphocytes (TILs) are being readily investigated. In this proof of concept study, we aim to explore the feasibility of using spatial lipidomics by MALDI-MSI to distinguish CRC tissue based upon their TIL content. Formalin-fixed paraffin-embedded tissue from human thymus and tonsil was first analysed by MALDI-MSI to obtain a curated mass list from a pool of single positive T lymphocytes, whose putative identities were annotated using an LC-MS-based lipidomic approach. A CRC tissue microarray (TMA, <i>n</i> = 30) was then investigated to determine whether these cases could be distinguished based upon their TIL content in the tumour and its microenvironment. MALDI-MSI from the pool of mature T lymphocytes resulted in the generation of a curated mass list containing 18 annotated <i>m</i>/<i>z</i> features. Initially, subsets of T lymphocytes were then distinguished based on their state of maturation and differentiation in the human thymus and tonsil tissue. Then, when applied to a CRC TMA containing differing amounts of T lymphocyte infiltration, those cases with a high TIL content were distinguishable from those with a lower TIL content, especially within the tumour microenvironment, with three lipid signals being shown to have the greatest impact on this separation (<i>p</i> < 0.05). On the whole, this preliminary study represents a promising starting point and suggests that a lipidomics MALDI-MSI approach could be a promising tool for subtyping the diverse immune environments in CRC.https://www.mdpi.com/2218-1989/11/9/599MALDI-MSIlipidomicscolorectal cancerlymphocytesimmunity
spellingShingle Vanna Denti
Allia Mahajneh
Giulia Capitoli
Francesca Clerici
Isabella Piga
Lisa Pagani
Clizia Chinello
Maddalena Maria Bolognesi
Giuseppe Paglia
Stefania Galimberti
Fulvio Magni
Andrew Smith
Lipidomic Typing of Colorectal Cancer Tissue Containing Tumour-Infiltrating Lymphocytes by MALDI Mass Spectrometry Imaging
Metabolites
MALDI-MSI
lipidomics
colorectal cancer
lymphocytes
immunity
title Lipidomic Typing of Colorectal Cancer Tissue Containing Tumour-Infiltrating Lymphocytes by MALDI Mass Spectrometry Imaging
title_full Lipidomic Typing of Colorectal Cancer Tissue Containing Tumour-Infiltrating Lymphocytes by MALDI Mass Spectrometry Imaging
title_fullStr Lipidomic Typing of Colorectal Cancer Tissue Containing Tumour-Infiltrating Lymphocytes by MALDI Mass Spectrometry Imaging
title_full_unstemmed Lipidomic Typing of Colorectal Cancer Tissue Containing Tumour-Infiltrating Lymphocytes by MALDI Mass Spectrometry Imaging
title_short Lipidomic Typing of Colorectal Cancer Tissue Containing Tumour-Infiltrating Lymphocytes by MALDI Mass Spectrometry Imaging
title_sort lipidomic typing of colorectal cancer tissue containing tumour infiltrating lymphocytes by maldi mass spectrometry imaging
topic MALDI-MSI
lipidomics
colorectal cancer
lymphocytes
immunity
url https://www.mdpi.com/2218-1989/11/9/599
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